Oncolytic Vaccinia Virus Expressing the Human Somatostatin Receptor SSTR2: Molecular Imaging after Systemic Delivery Using 111In-Pentetreotide
Bibliographic record
Abstract
Oncolytic vaccinia viruses (VV) have demonstrated tumor specificity, high levels of transgene expression, and anti-tumor effects. The ability to visualize vector biodistribution noninvasively will be necessary as gene therapy vectors come to clinical trials, and the creation of a VV that can both treat tumors and permit noninvasive imaging after systemic delivery is therefore an exciting concept. To facilitate imaging, a VV expressing the human somatostatin receptor type 2 (SSTR2) was created. Cells infected with the SSTR2-expressing VV or controls were incubated with the somatostatin analog 111In-pentetreotide with or without an excess of nonradiolabeled pentetreotide. The SSTR2-infected cells bound 111In-pentetreotide sixfold more efficiently than control virus-infected cells and this binding was specifically blocked by nonradiolabeled pentetreotide. Nude mice bearing subcutaneous murine colon CA xenografts were injected intraperitoneally with the SSTR2-expressing VV or control VV. After 6 days, mice were injected with 111In-pentetreotide and imaged. Mice were sacrificed and organs collected and counted in a gamma counter. The uptake of radioactivity in tumors and normal tissues (percentage injected dose per gram) and tumor-to-normal tissue ratios were determined. Tumors infected with the SSTR2-expressing VV accumulated significantly higher concentrations of radioactivity compared to tumors in animals receiving the control virus. SSTR2-infected tumors were visible on imaging 6 days after VV injection and could be visualized for up to 3 weeks post-viral injection using repeat injections of 111In-pentetreotide. This reporter gene imaging strategy could be a very effective method to visualize vector distribution, expression, and persistence over time and enhances the potential of VV as a novel anti-cancer therapeutic.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".